(1) Chesney J (2) Lewis KD (3) Kluger H (4) Hamid O (5) Whitman E (6) Thomas S (7) Wermke M (8) Cusnir M (9) Domingo-Musibay E (10) Phan GQ (11) Kirkwood JM (12) Hassel JC (13) Orloff M (14) Larkin J (15) Weber J (16) Furness AJS (17) Khushalani NI (18) Medina T (19) Egger ME (20) Graf Finckenstein F (21) Jagasia M (22) Hari P (23) Sulur G (24) Shi W (25) Wu X (26) Sarnaik A

Journal for immunotherapy of cancer

BACKGROUND: Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2_cell therapy trial in melanoma. METHODS: Eligible patients had advanced melanoma that progressed after ICI and targeted therapy, where appropriate. Melanoma lesions were resected (resected tumor diameter ³1.5_cm) and shipped to a central good manufacturing practice facility for 22-day lifileucel manufacturing. Patients received a non-myeloablative lymphodepletion regimen, a single lifileucel infusion, and up to six doses of high-dose interleukin-2. The primary endpoint was IRC-assessed ORR (Response Evaluation Criteria in Solid Tumors V.1.1). RESULTS: The Full Analysis Set consisted of 153 patients treated with lifileucel, including longer-term follow-up on the 66 patients previously reported. Patients had received a median of 3.0 lines of prior therapy (81.7% received both anti-programmed cell death protein 1 and anti-cytotoxic lymphocyte-associated protein 4) and had high disease burden at baseline (median target lesion sum of diameters (SOD): 97.8_mm; lactate dehydrogenase (LDH) >upper limit of normal: 54.2%). ORR was 31.4% (95% CI: 24.1% to 39.4%), with 8 complete responses and 40 partial responses. Median duration of response was not reached at a median study follow-up of 27.6 months, with 41.7% of the responses maintained for ³18 months. Median overall survival and progression-free survival were 13.9 and 4.1 months, respectively. Multivariable analyses adjusted for Eastern Cooperative Oncology Group performance status demonstrated that elevated LDH and target lesion SOD >median were independently correlated with ORR (p=0.008); patients with normal LDH and SOD

Author Info: (1) Department of Medicine, University of Louisville, Louisville, Kentucky, USA. (2) Medical Oncology, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, USA. (3)

Author Info: (1) Department of Medicine, University of Louisville, Louisville, Kentucky, USA. (2) Medical Oncology, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, USA. (3) Medical Oncology, Hematology & Oncology, Melanoma and Onco-Dermatology, Genitourinary Oncology, Yale New Haven Health Smilow Cancer Hospital, New Haven, Connecticut, USA. (4) Hematology Oncology, The Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, California, USA. (5) Atlantic Health System Cancer Care, Morristown, New Jersey, USA. (6) Hematology and Oncology, Orlando Health Cancer Institute, Orlando, Florida, USA. (7) Technische UniversitŠt Dresden - NCT/UCC Early Clinical Trial Unit, Dresden, Sachsen, Germany. (8) Division of Hematology & Oncology, Mount Sinai Medical Center, Miami Beach, Florida, USA. (9) Division of Hematology, Oncology and Transplantation, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. (10) Surgery, Virginia Commonwealth University, Massey Cancer Center, Richmond, Virginia, USA. (11) Medicine, Dermatology and Translational Science, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. (12) Skin Cancer Center, UniversitŠt Heidelberg, Heidelberg, Baden-WŸrttemberg, Germany. (13) Thomas Jefferson University Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania, USA. (14) The Royal Marsden NHS Foundation Trust, London, UK. (15) Department of Medicine, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA. (16) The Royal Marsden NHS Foundation Trust, London, UK. (17) Department of Cutaneous Oncology, H Lee Moffitt Cancer Center, Tampa, Florida, USA. (18) Medical Oncology, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, USA. (19) Department of Medicine, University of Louisville, Louisville, Kentucky, USA. (20) Iovance Biotherapeutics Inc, San Carlos, California, USA. (21) Iovance Biotherapeutics Inc, San Carlos, California, USA. (22) Iovance Biotherapeutics Inc, San Carlos, California, USA. (23) Iovance Biotherapeutics Inc, San Carlos, California, USA. (24) Iovance Biotherapeutics Inc, San Carlos, California, USA. (25) Iovance Biotherapeutics Inc, San Carlos, California, USA. (26) Department of Cutaneous Oncology, H Lee Moffitt Cancer Center, Tampa, Florida, USA amod.sarnaik@moffitt.org.

Citation: J Immunother Cancer 2022 Dec 10: Epub

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/36600653

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